This project will evaluate the performance of new derivatization chemistry for amino acids and peptides. The derivatives will be designed to incorporate high-sensitivity, electrochemically active functional groups into the substrate so that liquid chromatography/electrochemistry (LCEC) may be used for separation and detection. Four reaction schemes are outlined, each with unique electrochemically-active functional groups and reactivities. Preliminary experiments with a modified o-phthalaldehyde system have demonstrated the separation of all primary amino acids in less than 10 minutes, a 3-10X improvement in speed with at least equivalent sensitivity to all previous methods. It is anticipated that: (1) LCEC will be capable of 0.05 picomole detection limits, (2) derivatization will be applicable to small peptides via the N-terminus, and (3) byproper design, the derivatives will be easily formed and stable over at least 60 minutes. Cyclic voltammetry and liquid chromatography/electrochemistry will be used to study reaction kinetics, derivative stability, electrochemistry, and chromatographic selectivity. The methods of choice will be tested in three physiological samples of biomedical importance: (1) amino acid composition in peptide hydrolysate of less than 100 picomoles, 92) detection of enkephalins in brain tissue, and (3) determination of free amino acids in plasma. In developing these methods, emphasis will be on simplicity, reliability, and economy. Systems based on LCEC and pre-column derivatization chemistry for peptides and amino acids will cost approximately $9000-15000, a factor of 2-3x less than the optical detection-based systems presently available. It is anticipated that such a system would benefit clinical chemists desiring a rapid amino acid system as well as neurochemists, nutritionists, and biochemists requiring a more versatile and sensitive approach to detecting peptides and amino acids.